Format

Send to

Choose Destination
BMC Complement Altern Med. 2015 Jun 6;15:165. doi: 10.1186/s12906-015-0681-9.

A lupane-triterpene isolated from Combretum leprosum Mart. fruit extracts that interferes with the intracellular development of Leishmania (L.) amazonensis in vitro.

Author information

1
Malaria and Leishmaniasis Bioassays platform, Oswaldo Cruz Foundation (Fiocruz Rondônia), Porto Velho, Rondônia, Brazil. carolinateles@fiocruz.br.
2
Center of Studies for Biomolecules Applied to Health (CEBio), Oswaldo Cruz Foundation (Fiocruz Rondônia), Porto Velho, Rondônia, Brazil. leandroqmc@hotmail.com.
3
Laboratory of Insect Bioecology, Universidade Federal de Rondônia (UNIR), Porto Velho, Rondônia, Brazil. alealsil@unir.br.
4
Laboratory of Medical Entomology, Oswaldo Cruz Foundation (Fiocruz Rondônia), Porto Velho, Rondônia, Brazil. alealsil@unir.br.
5
Research Laboratory of Chemistry of Natural Products, Universidade Federal de Rondônia (UNIR), Porto Velho, Rondônia, Brazil. vfacundo@unir.br.
6
Structural Biochemistry Laboratory, PUC, Rio Grande do Sul, Porto Alegre, Brazil. walter@azevedolab.net.
7
Laboratory of Molecular Epidemiology, Research Institute for Tropical Diseases in Rondônia (IPEPATRO), Porto Velho, Rondônia, Brazil. isjcavalli@uesc.br.
8
Laboratory of Cellular Ultrastructure Hertha Meyer, Institute of Biophysics, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil. motta@biof.ufrj.br.
9
Center of Studies for Biomolecules Applied to Health (CEBio), Oswaldo Cruz Foundation (Fiocruz Rondônia), Porto Velho, Rondônia, Brazil. stabeli@fiocruz.br.
10
Department of Biological Sciences, Universidade Estadual de Santa Cruz (UESC), Ilheús, Bahia, Brazil. isjcavalli@uesc.br.

Abstract

BACKGROUND:

3beta,6beta,16beta-trihydroxylup-20(29)-ene is a lupane triterpene isolated from Combretum leprosum fruit. The lupane group has been extensively used in studies on anticancer effects; however, its possible activity against protozoa parasites is yet poorly known. The high toxicity of the compounds currently used in leishmaniasis chemotherapy stimulates the investigation of new molecules and drug targets for antileishmanial therapy.

METHODS:

The activity of 3beta,6beta,16beta-trihydroxylup-20(29)-ene was evaluated against Leishmania (L.) amazonensis by determining the cytotoxicity of the compound on murine peritoneal macrophages, as well as its effects on parasite survival inside host cells. To evaluate the effect of this compound on intracellular amastigotes, cultures of infected macrophages were treated for 24, 48 and 96 h and the percentage of infected macrophages and the number of intracellular parasites was scored using light microscopy.

RESULTS:

Lupane showed significant activity against the intracellular amastigotes of L. (L.) amazonensis. The treatment with 109 μM for 96 h reduced in 80 % the survival index of parasites in BALB/c peritoneal macrophages. At this concentration, the triterpene caused no cytotoxic effects against mouse peritoneal macrophages. Ultrastructural analyses of L. (L.) amazonensis intracellular amastigotes showed that lupane induced some morphological changes in parasites, such as cytosolic vacuolization, lipid body formation and mitochondrial swelling. Bioinformatic analyses through molecular docking suggest that this lupane has high-affinity binding with DNA topoisomerase.

CONCLUSION:

Taken together, our results have showed that the lupane triterpene from C. leprosum interferes with L. (L.) amazonensis amastigote replication and survival inside vertebrate host cells and bioinformatics analyses strongly indicate that this molecule may be a potential inhibitor of topoisomerase IB. Moreover, this study opens major prospects for the development of novel chemotherapeutic agents with leishmanicidal activity.

PMID:
26048712
PMCID:
PMC4457080
DOI:
10.1186/s12906-015-0681-9
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center